Strategies to change risk perceptions are a models of health decision making. Both are based on an assumption that may not always be true - that individuals know their risk for a given illness. Preliminary work from our and other laboratories has shown that a non-trivial portion of the population is uncertain about their risk for common illnesses. Moreover, we have shown that uncertainty about one's illness risk is particularly likely among U.S. populations who suffer the burden of health disparities. However, the mechanisms underlying risk uncertainty remain unknown, which limits our ability to develop effective intervention strategies to change behavior, especially in those who remain uncertain about their risk despite the wide-spread dissemination of risk-based health messaging. The objective for this R01 program of research is to explicate the mechanisms leading individuals to answer do not know in response to risk perception questions. In a program of research encompassing both observational and experimental work, we will examine how factors relating to knowledge and health literacy as well as factors related to defensive information avoidance influence do not know responding. This objective will be achieved by addressing two specific aims: 1) To explore two distinct, theoretically-informed explanations for do not know responding, and 2) To test whether experimentally manipulating the mechanisms hypothesized to cause do not know responding, reduces do not know responding. Aim 1 will be achieved with a national survey examining if low health literacy and defensive risk information avoidance are related to do not know responding to colorectal cancer and type 2 diabetes risk perception items. Achieving Aim 2 will be accomplished by experimentally testing 1) whether giving do not know responders with low health literacy health messages tailored to a low health literacy audience increases risk knowledge and reduces do not know responding and 2) whether giving do not know responders who tend to avoid health information the opportunity to self-affirm prior to receiving health messages increases attending to, and comprehension of these messages and reduces do not know responding. This research is significant in that it examines a key, but understudied phenomenon related to a central decision making and behavior change construct, uncertainty about perceived risk for illness. Successful completion of the proposed research will generate tested strategies for developing more effective behavior change messages for individuals who are uncertain about their risk for common illnesses. Given the degree to which uncertainty about illness risk is more common in groups experiencing health disparities populations, our work has the potential to address behavior change factors that contribute to these ongoing health disparities.